Urinary tract infections (UTI) are among the most common infections in humans which can be asymptomatic or cause cystitis, acute pyelonephritis and blood stream invasion. About 80% of UTIs in otherwise normal urinary tracts, the incidence of UTI is much higher and is caused by a wider spectrum of organisms; among these, Proteus mirabilis assumes importance not only because of its production of renal stones. Among patients with catheters or other foreign devices in the urinary tract, Candidate infections are becoming increasingly prominent. In this PO1, a group of accomplished and resource investigators has the following objectives: 1) to discover the mechanisms of pathogenesis of UT1 caused by E. coli, P. mirabilis. Our strategy is to use the powerful tools of molecular biology and a well established mouse model of UTI to examine known virulence factors and, via new techniques including signature tagged mutagenesis and in vivo expression technology, heretofore unknown virulence factors. Similar resources will be used to develop candidate vaccines assembled from P. mirabilis subunits. This work will be done in the context of a strong history in infectious diseases, particularly molecular pathogenesis and vaccine development.